The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men.

Abstract

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and after treatment with either amlodipine (5 mg) or placebo capsule twice daily for 7 days by determining serum insulin, glucose, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and cortisol in the fasting state and during an oral glucose tolerance test. Amlodipine treatment 1) lowered fasting serum insulin (from 273 +/- 19 to 200 +/- 17 pmol/L; P < 0.0005) and glucose (from 5.4 +/- 0.1 to 5.1 +/- 0.1 mmol/L; P < 0.02), 2) reduced the area under the curve for glucose (from 1342 +/- 25 to 1198 +/- 23 mmol/L.min; P = 0.0001) and the area under the curve for insulin (from 155.5 +/- 7.8 to 103.9 +/- 4.3 nmol/L.min; P = 0.0001) during the oral glucose tolerance test, 3) increased fasting serum DHEA-S (from 5.19 +/- 0.37 to 7.95 +/- 0.58 mumol/L; P = 0.0001) and androstenedione (from 5.65 +/- 0.65 to 6.83 +/- 0.53 nmol/L; P < 0.01), and 4) decreased fasting serum cortisol (from 538 +/- 35 to 494 +/- 26 nmol/L; P < 0.05). Fasting serum androstenedione declined slightly in the placebo group (from 5.96 +/- 0.60 to 5.74 +/- 0.57 nmol/L; P < 0.005), but no change occurred in glucose tolerance, fasting serum DHEA-S, or cortisol. We conclude that amlodipine treatment improves glucose tolerance, reduces fasting and glucose-stimulated serum insulin levels, increases serum DHEA-S and androstenedione levels, and decreases circulating cortisol.